Daptomycin and AgNP co-loaded rGO nanocomposites for specific treatment of Gram-positive bacterial infection in vitro and in vivo

2019 ◽  
Vol 7 (12) ◽  
pp. 5097-5111 ◽  
Author(s):  
Chunyi Tong ◽  
Li Li ◽  
Feng Xiao ◽  
Jialong Fan ◽  
Xianghua Zhong ◽  
...  

rGO was used for simultaneously anchoring AgNPs and Daptomycin to prepare rGO@Ag@Dap for anti-bacterium. The new nanomaterial showed strong Gram-positive bacteria killing ability in vitro and enhanced wound healing infected with S. aureus in vivo.

2006 ◽  
Vol 50 (6) ◽  
pp. 2261-2264 ◽  
Author(s):  
Hee-Soo Park ◽  
Hyun-Joo Kim ◽  
Min-Jung Seol ◽  
Dong-Rack Choi ◽  
Eung-Chil Choi ◽  
...  

ABSTRACT DW-224a showed the most potent in vitro activity among the quinolone compounds tested against clinical isolates of gram-positive bacteria. Against gram-negative bacteria, DW-224a was slightly less active than the other fluoroquinolones. The in vivo activities of DW-224a against gram-positive bacteria were more potent than those of other quinolones.


2005 ◽  
Vol 49 (6) ◽  
pp. 2498-2500 ◽  
Author(s):  
Eun Jeong Yoon ◽  
Yeong Woo Jo ◽  
Sung Hak Choi ◽  
Tae Ho Lee ◽  
Jae Keol Rhee ◽  
...  

ABSTRACT In vitro and in vivo activities of DA-7867 were assessed against methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and penicillin-resistant Streptococcus pneumoniae. All isolates were inhibited by DA-7867 at ≤0.78 μg/ml, a four-times-lower concentration than that of inhibition by linezolid. For murine infection models, DA-7867 also exhibited greater efficacy than linezolid against all isolates tested.


2015 ◽  
Vol 25 (2-3) ◽  
pp. 79-93 ◽  
Author(s):  
Joseph W. Lengeler

<b><i>Past:</i></b> The title ‘PTS 50 or The PTS after 50 years' relies on the first description in 1964 of the phosphoenolpyruvate-dependent carbohydrate:phosphotransferase system (PTS) by Kundig, Gosh and Roseman [Proc Natl Acad Sci USA 1964;52:1067-1074]. The system comprised proteins named Enzyme I, HPr and Enzymes II, as part of a novel PTS for carbohydrates in Gram-negative and Gram-positive bacteria, whose ‘biological significance remained unclear'. In contrast, studies which would eventually lead to the discovery of the central role of the PTS in bacterial metabolism had been published since before 1942. They are primarily linked to names like Epps and Gale, J. Monod, Cohn and Horibata, and B. Magasanik, and to phenomena like ‘glucose effects', ‘diauxie', ‘catabolite repression' and carbohydrate transport. <b><i>Present:</i></b> The pioneering work from Roseman's group initiated a flood of publications. The extraordinary progress from 1964 to this day in the qualitative and in vitro description of the genes and enzymes of the PTS, and of its multiple roles in global cellular control through ‘inducer exclusion', gene induction and ‘catabolite repression', in cellular growth, in cell differentiation and in chemotaxis, as well as the differences of its functions between Gram-positive and Gram-negative bacteria, was one theme of the meeting and will not be treated in detail here. <b><i>Future:</i></b> At the 1988 Paris meeting entitled ‘The PTS after 25 years', Saul Roseman predicted that ‘we must describe these interactions [of the PTS components] in a quantitative way [under] in vivo conditions'. I will present some results obtained by our group during recent years on the old phenomenon of diauxie by means of very fast and quantitative tests, measured in vivo, and obtained from cultures of isogenic mutant strains growing under chemostat conditions. The results begin to hint at the problems relating to future PTS research, but also to the ‘true science' of Roseman.


RSC Advances ◽  
2014 ◽  
Vol 4 (99) ◽  
pp. 56031-56040 ◽  
Author(s):  
Ilaria Rago ◽  
Chandrakanth Reddy Chandraiahgari ◽  
Maria P. Bracciale ◽  
Giovanni De Bellis ◽  
Elena Zanni ◽  
...  

ZnO micro and nanorods, produced through simple and inexpensive techniques, resulted to be strong antimicrobials against Gram-positive bacteria, in vitro as well as in vivo, by altering cell outer structures like membrane and exopolysaccharides.


2011 ◽  
Vol 79 (9) ◽  
pp. 3596-3606 ◽  
Author(s):  
Chris S. Rae ◽  
Aimee Geissler ◽  
Paul C. Adamson ◽  
Daniel A. Portnoy

ABSTRACTListeria monocytogenesis a Gram-positive intracellular pathogen that is naturally resistant to lysozyme. Recently, it was shown that peptidoglycan modification by N-deacetylation or O-acetylation confers resistance to lysozyme in various Gram-positive bacteria, includingL. monocytogenes.L. monocytogenespeptidoglycan is deacetylated by the action ofN-acetylglucosamine deacetylase (Pgd) and acetylated byO-acetylmuramic acid transferase (Oat). We characterized Pgd−, Oat−, and double mutants to determine the specific role ofL. monocytogenespeptidoglycan acetylation in conferring lysozyme sensitivity during infection of macrophages and mice. Pgd−and Pgd−Oat−double mutants were attenuated approximately 2 and 3.5 logs, respectively,in vivo. In bone-marrow derived macrophages, the mutants demonstrated intracellular growth defects and increased induction of cytokine transcriptional responses that emanated from a phagosome and the cytosol. Lysozyme-sensitive mutants underwent bacteriolysis in the macrophage cytosol, resulting in AIM2-dependent pyroptosis. Each of thein vitrophenotypes was rescued upon infection of LysM−macrophages. The addition of extracellular lysozyme to LysM−macrophages restored cytokine induction, host cell death, andL. monocytogenesgrowth inhibition. This surprising observation suggests that extracellular lysozyme can access the macrophage cytosol and act on intracellular lysozyme-sensitive bacteria.


2000 ◽  
Vol 68 (3) ◽  
pp. 1600-1607 ◽  
Author(s):  
Andreas Sing ◽  
Thomas Merlin ◽  
Hans-Peter Knopf ◽  
Peter J. Nielsen ◽  
Harald Loppnow ◽  
...  

ABSTRACT We investigated the reason for the inability of lipopolysaccharide (LPS)-resistant (Lps-defective [Lpsd ]) C57BL/10ScCr mice to produce beta interferon (IFN-β) when stimulated with bacteria. For this purpose, the IFN-β and other macrophage cytokine responses induced by LPS and several killed gram-negative and gram-positive bacteria in LPS-sensitive (Lps-normal [Lpsn ]; C57BL/10ScSn and BALB/c) and Lpsd (C57BL/10ScCr and BALB/c/l) mice in vitro and in vivo were investigated on the mRNA and protein levels. In addition, double-stranded RNA (dsRNA) was used as a nonbacterial stimulus. LPS and all gram-negative bacteria employed induced IFN-β in the Lpsn mice but not in theLpsd mice. All gram-positive bacteria tested failed to induce significant amounts of IFN-β in all four of the mouse strains used. As expected, all other cytokines tested (tumor necrosis factor alpha, interleukin 1α [IL-1α], IL-6, and IL-10) were differentially induced by gram-negative and gram-positive bacteria. Stimulation with dsRNA induced IFN-β and all other cytokines mentioned above in all mouse strains, regardless of their LPS sensitivities. The results suggest strongly that LPS is the only bacterial component capable of inducing IFN-β in significant amounts that are readily detectable under the conditions used in this study. Consequently, in mice, IFN-β is inducible only by gram-negative bacteria, but not in C57BL/10ScCr or other LPS-resistant mice.


eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Alison C McKelvey ◽  
Travis B Lear ◽  
Sarah R Dunn ◽  
John Evankovich ◽  
James D Londino ◽  
...  

Toll-like receptor 2 (TLR2) is a pattern recognition receptor that recognizes many types of PAMPs that originate from gram-positive bacteria. Here we describe a novel mechanism regulating TLR2 protein expression and subsequent cytokine release through the ubiquitination and degradation of the receptor in response to ligand stimulation. We show a new mechanism in which an uncharacterized RING finger E3 ligase, PPP1R11, directly ubiquitinates TLR2 both in vitro and in vivo, which leads to TLR2 degradation and disruption of the signaling cascade. Lentiviral gene transfer or knockdown of PPP1R11 in mouse lungs significantly affects lung inflammation and the clearance of Staphylococcus aureus. There is a negative correlation between PPP1R11 and TLR2 levels in white blood cell samples isolated from patients with Staphylococcus aureus infections. These results suggest that PPP1R11 plays an important role in regulating innate immunity and gram-positive bacterial clearance by functioning, in part, through the ubiquitination and degradation of TLR2.


Microbiology ◽  
2010 ◽  
Vol 156 (12) ◽  
pp. 3532-3543 ◽  
Author(s):  
Geoff P. Doherty ◽  
Mark J. Fogg ◽  
Anthony J. Wilkinson ◽  
Peter J. Lewis

Bacterial RNA polymerases (RNAPs) contain several small auxiliary subunits known to co-purify with the core α, β and β′ subunits. The ω subunit is conserved between Gram-positive and Gram-negative bacteria, while the δ subunit is conserved within, but restricted to, Gram-positive bacteria. Although various functions have been assigned to these subunits via in vitro assays, very little is known about their in vivo roles. In this work we constructed a pair of vectors to investigate the subcellular localization of the δ and ω subunits in Bacillus subtilis with respect to the core RNAP. We found these subunits to be closely associated with RNAP involved in transcribing both mRNA and rRNA operons. Quantification of these subunits revealed δ to be present at equimolar levels with RNAP and ω to be present at around half the level of core RNAP. For comparison, the localization and quantification of RNAP β′ and ω subunits in Escherichia coli was also investigated. Similar to B. subtilis, β′ and ω closely associated with the nucleoid and formed subnucleoid regions of high green fluorescent protein intensity, but, unlike ω in B. subtilis, ω levels in E. coli were close to parity with those of β′. These results indicate that δ is likely to be an integral RNAP subunit in Gram-positives, whereas ω levels differ substantially between Gram-positives and -negatives. The ω subunit may be required for RNAP assembly and subsequently be turned over at different rates or it may play roles in Gram-negative bacteria that are performed by other factors in Gram-positives.


2009 ◽  
Vol 43 (5) ◽  
pp. 928-938 ◽  
Author(s):  
Lisa Charneski ◽  
Priti N Patel ◽  
Donna Sym

Objective To review the pharmacology, antimicrobial activity, pharmacokinetics, clinical applications, and safety of telavancin, a new lipoglycopeptide antibiotic. Data Sources Literature was obtained from MEDLINE (1966–April 2009) and International Pharmaceutical Abstracts (1971–April 2009) using the search terms telavancin and TD-6424, and also from Theravance, Inc., and Astellas Pharma US, Inc. Study Selection And Data Extraction Available English-language articles were reviewed, as well as information obtained from Theravance, Inc., and Astellas Pharma US, Inc. Data Synthesis Telavancin has rapid bactericidal activity against gram-positive aerobic and anaerobic bacteria through multiple mechanisms of action. In vitro and Phase 2 in vivo data support the efficacy of telavancin against antibiotic-resistant gram-positive organisms. On March 4, 2008, the Food and Drug Administration (FDA) accepted as complete for review Theravance's response to the October 19, 2007, New Drug Application approvable letter for telavancin to be used as treatment for complicated skin and skin structure infections (cSSSIs) caused by gram-positive bacteria. QTc interval prolongation has been reported, although the clinical impact of this has not been determined. Drug interactions have not been identified as of yet. Conclusions Telavancin is currently under review by the FDA for the treatment of cSSSIs caused by gram-positive bacteria. The completion of Phase 3 trials will determine whether telavancin will have a role in the treatment of other infections caused by resistant gram-positive bacteria.


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